title: Epigenetic control of embryonic renal cell differentiation by L1 retrotransposon.
abstract: BACKGROUND
  L1 retroelements may play a central role in morphogenesis through epigenetic mechanisms involving recruitment of chromatin modifying protein complexes. Retroelements are repressed in terminally differentiated cells, and highly active in embryonic, undifferentiated, and transformed cells. It is not clear if the modulation of differentiation by L1 is a "cause" or "effect". The purpose of this study was to determine if murine embryonic kidney cells of clonal origin (mK4 cells) harbor retrotransposition events upon ectopic expression of L1, and the impact of L1 on embryonic kidney cell differentiation. Given that L1 is reactivated by aryl hydrocarbon receptor (AHR) ligands, we also sought to investigate the effects of benzo(a)pyrene (BaP) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on the genetic network of mK4 cells.
  
  
  METHODS
  The mK4 cells overexpressing human L1(RP) were assessed for changes in proliferation and expression of molecular markers of cellular differentiation.
  
  
  RESULTS
  L1(RP) increased proliferation rates and markedly downregulated differentiation programming in mK4 cells. These genetic alterations were recapitulated by exogenous activation of L1 by AHR ligands.
  
  
  CONCLUSIONS
  L1 regulates nephrogenesis in vitro via both insertional and non-insertional mechanisms that disrupt mesenchymal to epithelial transition. Thus, a feedback loop involving L1, WT1, and AHR may play a role in regulation of kidney morphogenesis. Birth Defects Research (Part A), 2011. © 2011 Wiley-Liss, Inc.
authors.affiliation: Department of Biochemistry and Molecular Biology and Center for Genetics and Molecular Medicine, School of Medicine, University of Louisville, Louisville, KY 40202, USA. Kenneth.ramos@louisville.edu
authors.forename: Kenneth S
authors.initials: KS
authors.lastname: Ramos
authors.forename: Diego E
authors.initials: DE
authors.lastname: Montoya-Durango
authors.forename: Ivo
authors.initials: I
authors.lastname: Teneng
authors.forename: Adrian
authors.initials: A
authors.lastname: Nanez
authors.forename: Vilius
authors.initials: V
authors.lastname: Stribinskis
mesh_terms: D000818:Animals; D001564:Benzo(a)pyrene / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D044127:Epigenesis, Genetic; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D053263:Gene Regulatory Networks / Q000187:drug effects; D007668:Kidney / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D051379:Mice; D009024:Morphogenesis / Q000187:drug effects; D000072317:Polychlorinated Dibenzodioxins / Q000494:pharmacology; D018336:Receptors, Aryl Hydrocarbon / Q000235:genetics / Q000378:metabolism; D018626:Retroelements / Q000187:drug effects*
chemical_list: D000072317:Polychlorinated Dibenzodioxins; D018336:Receptors, Aryl Hydrocarbon; D018626:Retroelements; D001564:Benzo(a)pyrene